On the basis of the thoughts and summaries of doctors of the past dynasties，the connotation and denotation of liver governing free flow of qi have been continuously enriched and expanded，which gradually developed from single dredging and excreting to various multi-system physiological functions，such as regulating emotions，qi and blood as well as spleen and stomach，excreting bile，dredging water channels，and regulating reproduction.In traditional Chinese medicine(TCM) theory，liver and brain are particularly closed，mainly reflected in the three aspects of life activity，mental activity and sensory and motor activity.On this basis，this paper，by integrating the relevant research and the latest progress in recent years，elucidated the modern biological regulatory mechanism of liver governing free flow of qi as follows:The control system of liver governing free flow of qi was the limbic system of the brain，by the way of neuro-endocrine-immune network represented by hypothalamic-pituitary-adrenal axis and microbiome-gut-brain axis，and acting on muscle tissues represented by smooth muscle of internal organs and blood vessels and skeletal muscle.Further explaining the scientific connotation of liver governing free flow of qi is conducive to broadening its research ideas，which provides theoretical basis for clinical application.